ABSTRACT
Novel coronavirus disease (COVID-19) can have variety of cardiac manifestations; however, less is known about the prevalence, clinical characteristics and outcomes of bradyarrhythmias in patients with COVID-19. In the present case series of bradyarrhythmia in patients with COVID-19, we report complete heart block requiring intervention in 5 patients and sinus node dysfunction in 2 patients.
ABSTRACT
A novel series of o-phenylenediamine-based inhibitors of indoleamine 2,3-dioxygenase (IDO) has been identified. IDO is a heme-containing enzyme, overexpressed in the tumor microenvironment of many cancers, which can contribute to the suppression of the host immune system. Synthetic modifications to a previously described diarylether series resulted in an additional degree of molecular diversity which was exploited to afford compounds that demonstrated significant potency in the HeLa human cervical cancer IDO1 assay. .
Subject(s)
Enzyme Inhibitors/pharmacology , Indoleamine-Pyrrole 2,3,-Dioxygenase/antagonists & inhibitors , Phenylenediamines/pharmacology , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/metabolism , HeLa Cells , Humans , Microsomes, Liver/metabolism , Phenylenediamines/chemical synthesis , Phenylenediamines/chemistry , Phenylenediamines/metabolism , Structure-Activity RelationshipABSTRACT
Substitution of exogenous (-)-sparteine for a more practical achiral base in the aerobic oxidative kinetic resolution of secondary alcohols is described. Carbonate bases are the most effective of those screened and allow for effective kinetic resolution of benzylic, allylic, and aliphatic substrates. The procedure was also successfully extended to the oxidative desymmetrization of meso diols.
Subject(s)
Alcohols/chemistry , Alcohols/isolation & purification , Catalysis , Kinetics , Oxygen/chemistry , Palladium/chemistry , Sparteine/chemistryABSTRACT
Evaluation of the substrate scope for Pd(II)/ (-)-sparteine catalyzed aerobic oxidative kinetic resolution of secondary alcohols is disclosed. An improved system is found with use of tert-butyl alcohol solvent in which benzylic and aliphatic alcohols as well as alcohols containing olefins are effectively oxidatively resolved. For substrates that successfully undergo oxidative kinetic resolution, k(rel) values are generally between 10 and 20. Successful scale-up of various substrates to 10-mmol scale is described. Extension to oxidative desymmetrization of 1,3-meso-diols is successful with enantiomeric excesses ranging from 78 to 85%.
Subject(s)
Alcohols/chemistry , Palladium/chemistry , Sparteine/chemistry , Alcohols/analysis , Catalysis , Kinetics , Magnetic Resonance Spectroscopy , Molecular Structure , Oxidation-Reduction , StereoisomerismABSTRACT
Formation of distinctly different products from the same alkoxide intermediate indicates a strong dependence of reaction pathways on counterions.
